Drug Delivery and Translational Research最新文献

{"title":"Post-encapsulation methods for the preparation of mRNA-LNPs.","authors":"Joanna Duffrène, Chloé Muzard, Johanne Seguin, Charlotte Izabelle, Thibaut Vrai, Tina Ejlalmanesh, Marianne Bombled, Samir Hamdi, Katia Lemdani, Khair Alhareth, Nathalie Mignet","doi":"10.1007/s13346-025-01866-0","DOIUrl":"https://doi.org/10.1007/s13346-025-01866-0","url":null,"abstract":"<p><p>Microfluidics mixing is the current lab-scale method used for producing mRNA-loaded lipid nanoparticles (mRNA-LNPs) thanks to reproducibility and robustness of microfluidic mixing. Despite these advantages, the production of small LNP volumes is associated with significant material waste. Given the high cost of synthetic mRNA, this waste can be a major limitation, particularly for early-stage screening of formulations. This study proposes alternative methods for mRNA-LNP formulation aiming to improve their stability for both formulation and mRNA screening, while reducing material waste on a research scale. Specifically, we investigated post-encapsulation of mRNA into pre-formed vesicles (PFVs) obtained by microfluidic mixing. These PFVs were complexed with mRNA by: (1) a microfluidic or (2) a manual pipetting method. The resulting mRNA-LNPs produced using these two post-encapsulation methods exhibit similar physicochemical properties and morphologies to those obtained by conventional microfluidic protocol. These mRNA-LNPs were assessed on in vitro and in vivo expression. mRNA-LNPs prepared by our alternative methods showed a similar transfection level compared to the conventional formulation taken as a control. The suitability of post-encapsulation methods to other lipids, mRNAs and microfluidic systems was also confirmed. This work offers robust, simple and economic alternative methods for preparing small volumes of mRNA-LNPs. The versatility of post-encapsulation methods allows to screen mRNA formulations in a wide range of laboratories. These methods could be applied to encapsulate tailored doses of mRNA and various mRNA constructs to achieve an optimal and personalized therapy.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Buccal application of microneedles coated with an optimized hydrogel containing naproxen and dexamethasone.","authors":"Joo-Young Kim, Yun-Sik Um, Young-Guk Na, Da-Eun Kim, Yo Han Song, Suyeon Hwang, Minki Jin, Jooyoung Kim, Seung-Ki Baek, Jong-Suep Baek, Hong-Ki Lee, Cheong-Weon Cho","doi":"10.1007/s13346-025-01870-4","DOIUrl":"https://doi.org/10.1007/s13346-025-01870-4","url":null,"abstract":"<p><p>Inflammation and impaired bone regeneration are major challenges in oral and maxillofacial surgery, necessitating the development of effective drug delivery systems. This study aimed to develop a hydrogel-based microneedle (MN) system for the controlled release of anti-inflammatory and osteogenic drugs. A hydrogel loaded with naproxen sodium (NAS) and dexamethasone sodium phosphate (DEX) using poloxamer 407 (NDgel) was prepared using a low-temperature method and optimized via the Box-Behnken design. The optimized hydrogel exhibited a gelation temperature of 30.87 ± 0.64℃, pH 7.92 ± 0.12, and viscosity 87.47 ± 5.66 cP. Physicochemical evaluations, including differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), confirmed that NAS and DEX were incorporated in an amorphous form. The hydrogel was coated onto microneedles (NDgMN) via a dip-coating method and dried. In vitro drug release studies in artificial saliva showed NAS and DEX release rates of 21.7 ± 5.8% and 19.0 ± 1.8%, respectively, after 5 min. The NDgMN exhibited significantly enhanced permeability, with 48.5% and 48.7% permeability for NAS and DEX after 48 h, compared to 31.0% and 28.8% for the hydrogel alone. The IC₅₀ values of the drug solution and drug-containing gel were 123 µg/mL and 203.2 µg/mL, respectively. NDgel demonstrated concentration-dependent inhibition of nitrogen oxide (NO) production at 1-1000 µg/mL, and alkaline phosphatase (ALP) activity assays revealed a 1.2-fold increase at concentrations above 50 µg/mL. These findings suggest that hydrogel-coated MNs have potential as a novel drug delivery system for reducing inflammation and promoting osteocyte differentiation due to their enhanced permeability and bioactivity.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S.C. delivery of ultra-high concentration (up to 500 mg/mL) protein microparticle suspensions: pharmacokinetics, efficacy, biodistribution, and immunogenicity.","authors":"Sadiqua Shadbar, Lisa Liu, Yi Tang, Farah Kabir, Shankul Vartak, Zishu Gui, Margaret Huck, Eric Weinstein, Moin Khwaja, Aniket Dehadrai, Tyler Carter, James Ivey, Chaitanya Sudrik, Paul Brown, Lyndon Charles, Daniel Dadon","doi":"10.1007/s13346-025-01856-2","DOIUrl":"https://doi.org/10.1007/s13346-025-01856-2","url":null,"abstract":"<p><p>A shift towards the subcutaneous (S.C.) delivery of protein therapeutics is enabling patient-centric at-home self-administration. To circumvent the volume constraints of the S.C. route of delivery, protein therapeutics are required to achieve ever higher concentrations to administer doses beyond 1 g. Aqueous technologies rarely concentrate above 175 mg/mL and endure syringability and stability complications. Elektrofi's novel non-aqueous microparticle suspensions enable such ultra-high concentration delivery of protein therapeutics subcutaneously. In this work, we demonstrate the bioequivalence of high-concentration suspensions compared to their aqueous counterparts in a rodent model. The 500 mg/mL concentration iteration of the injection was injectable in 20 s with forces below 20 N. We also demonstrate comparable subcutaneous clearance of the suspension test articles to the aqueous comparator. To the best of our knowledge, this work is the first to report comparable efficacy and immunogenicity of microparticle suspensions to the aqueous comparator formulation. The model commercially available reagents serve as a glimpse into the performance of the Elektrofi technology which is in the process of advancing into the clinic with a multitude of biopharma partnerships.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Choline-based ionic liquids enhance the dermal delivery of cyclosporine a for potential treatment of psoriasis.","authors":"Yang Li, Qin Yu, Yi Lu, Yanyun Ma, Jianping Qi, Zhongjian Chen, Quangang Zhu, Wei Wu","doi":"10.1007/s13346-024-01705-8","DOIUrl":"10.1007/s13346-024-01705-8","url":null,"abstract":"<p><p>Psoriasis is a prevalent chronic disease affecting 2-3% of the global population. Cyclosporine A (CyA) has been widely used with great promise in the treatment of moderate to severe psoriasis despite various side effects associated with its systemic administration. Topical administration of CyA circumvents systemic side effects; however, the poor water solubility and large molecular weight of CyA pose challenges for dermal delivery. In this study, choline-based ionic liquids (ILs) were used to enhance the dermal delivery of CyA for the potential treatment of psoriasis. All four ILs tested significantly improved the solubility of CyA, which was greater than that of the control group with dimethyl sulfoxide (DMSO) as a solubilizer (20%, w/w). The saturated solubility of CyA in two of the ILs, choline geranate ([Ch][Ge]) and choline ricinoleate ([Ch][Ra]), reached more than 90 mg/mL, and the solubilization capability of the ILs except [Ch][Ci] was resistant to water dilution. The negligible change in CyA content determined by high-performance liquid chromatography and the secondary structure detected by circular dichroism spectroscopy confirmed the stability of CyA in the ILs. At 4 h in the in vitro penetration test, the amount of CyA retained in the skin in the IL groups was slightly greater than that in the control group (20% DMSO). The water content of the ILs significantly affected their penetration ability. When the water content increased from 10 to 70%, the dermal delivery of CyA first increased, peaked at a water content of 30%, and then decreased. The dermal delivery ability of [Ch][Ge] and [Ch][Ra] with a water content of 70% was still comparable to that of 20% DMSO. Moreover, CyA-loaded ILs (0.5%, w/w) significantly relieved the symptoms of psoriasis in an imiquimod (IMQ)-induced mouse model, and the levels of inflammatory factors, including tumor necrosis factor α, interleukin 22 and interleukin 17, in the affected area were reduced by 71.7%, 75.6%, and 89.3%, respectively. The IL tested, choline sorbate ([Ch][So]), showed low cytotoxicity to human immortalized epidermal cells (HaCaT). After 7 days of consecutive application, [Ch][So] did not cause significant irritation. In conclusion, ILs demonstrate promising potential for the dermal delivery of CyA for the treatment of psoriasis.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1693-1706"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folic acid-conjugated bovine serum albumin-coated selenium-ZIF-8 core/shell nanoparticles for dual target-specific drug delivery in breast cancer.","authors":"Arghavan Adibifar, Maryam Salimi, Neda Rostamkhani, Zahra Karami, Abdol-Hakim Agh-Atabay, Kobra Rostamizadeh","doi":"10.1007/s13346-024-01714-7","DOIUrl":"10.1007/s13346-024-01714-7","url":null,"abstract":"<p><p>Methotrexate (MTX), a frequently used chemotherapeutic agent, has limited water solubility, leading to rapid clearance even in local injections. In the present study, we developed folic acid-conjugated BSA-stabilized selenium-ZIF-8 core/shell nanoparticles for targeted delivery of MTX to combat breast cancer. FT-IR, XRD, SEM, TEM, and elemental mapping analysis confirmed the successful formation of FA-BSA@MTX@Se@ZIF-8. The developed nano-DDS had a mean diameter, polydispersity index, and zeta potential of 254.8 nm, 0.17, and - 16.5 mV, respectively. The release behavior of MTX from the nanocarriers was pH-dependent, where the cumulative release percentage at pH 5.4 was higher than at pH 7.4. BSA significantly improved the blood compatibility of nanoparticles so that after modifying their surface with BSA, the percentage of hemolysis decreased from 12.67 to 5.12%. The loading of methotrexate in BSA@Se@ZIF-8 nanoparticles reduced its IC₅₀ on 4T1 cells from 40.29 µg/mL to 16.54 µg/mL, and by conjugating folic acid on the surface, this value even decreased to 12.27 µg/mL. In vivo evaluation of the inhibitory effect in tumor-bearing mice showed that FA-BSA@MTX@Se@ZIF-8 caused a 2.8-fold reduction in tumor volume compared to the free MTX, which is due to the anticancer effect of selenium nanoparticles, the pH sensitivity of ZIF-8, and the presence of folic acid on the surface as a targeting agent. More importantly, histological studies and animal body weight monitoring confirmed that developed nano-DDS does not have significant organ toxicity. Taking together, the incorporation of chemotherapeutics in folic acid-conjugated BSA-stabilized selenium-ZIF-8 nanoparticles may hold a significant impact in the field of future tumor management.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1786-1799"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing curcumin in a multifunctional biodegradable metal-organic framework (bio-MOF) for targeted colorectal cancer theranostics.","authors":"Maryam Babaei, Amir Abrishami, Sonia Iranpour, Amir Sh Saljooghi, Maryam M Matin","doi":"10.1007/s13346-024-01707-6","DOIUrl":"10.1007/s13346-024-01707-6","url":null,"abstract":"<p><p>Despite significant advancements in managing colorectal cancer (CRC), the issues of efficient diagnosis and targeted therapy remain demanding. To address these challenges and improve treatment outcomes while reducing the cost and side effects, there is a need for more effective theranostic systems that combine diagnostic techniques with therapeutic modalities. This study introduces a pioneering approach for the synthesis of a porous bio-MOF (biodegradable metal-organic framework) using iron as the metal component and curcumin as the pharmaceutical ingredient. Subsequently, the developed drug delivery system was equipped with the anticancer drug doxorubicin (DOX), coated with biocompatible polyethylene glycol (PEG), and targeted with a CRC-specific aptamer (EpCAM). The physicochemical characterization confirmed the successful synthesis of the bio-MOF, demonstrating high encapsulation efficiency and pH-dependent release of DOX. In vitro studies for anticancer activity, cellular uptake, and mechanism of cell death demonstrated that in the case of positive EpCAM HT-29 cells, Apt-PEG-MOF@DOX had enhanced internalization that resulted in massive apoptosis. In vivo studies of the nanoparticles were then conducted in immunocompromised C57BL/6 mice bearing HT-29 tumors. These studies showed that the targeted platform could induce efficient tumor regression with reduced systemic toxicity. The targeted bio-MOF also exhibited MRI imaging properties useful for monitoring tumors. Significantly, the biocompatibility of the introduced bio-MOF was enhanced by pursuing the green synthesis method, which does not engage toxic solvents and strong acids. Overall, this multimodal system acts diversely as a tumor imaging agent and a therapeutic delivery platform suitable for CRC theranostics.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1719-1738"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticles in the battle against Candida auris biofilms: current advances and future prospects.","authors":"Bahgat Fayed","doi":"10.1007/s13346-024-01749-w","DOIUrl":"10.1007/s13346-024-01749-w","url":null,"abstract":"<p><p>Candida auris has emerged as a significant global health threat due to its multidrug resistance and ability to form robust biofilms, particularly on medical devices and hospital surfaces. Biofilms protect C. auris from antifungal treatments and the host immune response, making infections persistent and difficult to control. This review explores the potential of nanoparticles to overcome the limitations of traditional antifungal therapies in combating C. auris biofilms. Nanoparticles, with their unique physicochemical properties, offer promising strategies to penetrate biofilm matrices, deliver antifungal agents, and disrupt biofilm structure. Various types of nanoparticles, including metallic, polymeric, lipid-based, and cyclodextrin-based, demonstrate enhanced biofilm penetration and antifungal activity. Their ability to generate reactive oxygen species, disrupt cell adhesion, and release antifungals in a controlled manner makes them ideal candidates for biofilm-targeted therapies. This review presents the current advancements in nanoparticle-based solutions, emphasizing the need for further research into their mechanisms of action, safety, and clinical application. By addressing the challenge of C. auris biofilms specifically, this review provides a critical synthesis of existing knowledge and identifies future directions for developing effective antifungal therapies using nanotechnology.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1496-1512"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral delivery of stabilized lipid nanoparticles for nucleic acid therapeutics.","authors":"Kanika Suri, Liam Pfeifer, Donna Cvet, Angela Li, Michael McCoy, Amit Singh, Mansoor M Amiji","doi":"10.1007/s13346-024-01709-4","DOIUrl":"10.1007/s13346-024-01709-4","url":null,"abstract":"<p><p>Gastrointestinal disorders originate in the gastrointestinal tract (GIT), and the therapies can benefit from direct access to the GIT achievable through the oral route. RNA molecules show great promise therapeutically but are highly susceptible to degradation and often require a carrier for cytoplasmic access. Lipid nanoparticles (LNPs) are clinically proven drug-delivery agents, primarily administered parenterally. An ideal Orally Delivered (OrD) LNP formulation should overcome the diverse GI environment, successfully delivering the drug to the site of action. A versatile OrD LNP formulation has been developed to encapsulate and deliver siRNA and mRNA in this paper. The formulations were prepared by the systematic addition of cationic lipid to the base LNP formulation, keeping the total of cationic lipid and ionizable lipid to 50 mol%. Biorelevant media stability depicted increased resistance to bile salt mediated destabilization upon the addition of the cationic lipid, however the in vitro efficacy data underscored the importance of the ionizable lipid. Based on this, OrD LNP was selected comprising of 20% cationic lipid and 30% ionizable lipid. Further investigation revealed the enhanced efficacy of OrD LNP in vitro after incubation in different dilutions of fasted gastric, fasted intestinal media, and mucin. Confocal imaging and flow cytometry confirmed uptake while in vivo studies demonstrated efficacy with siRNA and mRNA as payloads. Taken together, this research introduces OrD LNP to deliver nucleic acid locally to the GIT.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1755-1769"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo evaluation of in situ forming polyester implants for the extended release of carvedilol.","authors":"Samer R Abulateefeh, Raghad M Abuhamdan, Husam Saed, Mohammad Alsalem, Khaldoun Shnewer","doi":"10.1007/s13346-024-01706-7","DOIUrl":"10.1007/s13346-024-01706-7","url":null,"abstract":"<p><p>Polyester based in situ forming implants (ISFIs) are injectable long-acting drug delivery systems that offer a wide range of unique advantages. As a result of these advantages, two relatively high molecular weight, ester terminated grades of poly (D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide) (PLA) were evaluated for their ability (i) to form ISFIs loaded with carvedilol, and (ii) to control its release both in vitro and in vivo. At a polymeric concentration of 40% w/w, implant solutions were syringeable, injectable, and able to encapsulate carvedilol to a high degree (encapsulated drug% > 97%). When visualized using scanning electron microscopy (SEM), implants were found to have a dense thin surface atop porous sublayers. As for their in vitro evaluation, PLGA and PLA implants were able to maintain drug release over the course of 49 and 84 days, respectively. On the other hand, in vivo drug release from both implants was almost identical and lasted for only 42 days. This may be due to the overriding effect of the similar host environment at the injection site that diminished the effect of polymeric physiochemistry on phase inversion and drug release. Lastly, while the polymer-free drug/NMP solution completely released its drug content within the initial half hour in vitro, the formulation extended drug release in vivo. This could be due to a yet to be investigated interaction between carvedilol and NMP under in vivo conditions. These results cement the significance of formulating carvedilol loaded ISFIs for the management of chronic conditions.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1707-1718"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microneedle patch capable of dual drug release for drug delivery to brain tumors.","authors":"Robab Mousavi, Madjid Soltani, Mohammad Souri","doi":"10.1007/s13346-024-01696-6","DOIUrl":"10.1007/s13346-024-01696-6","url":null,"abstract":"<p><p>Primary brain tumors are mostly managed using surgical resection procedures. Nevertheless, in certain cases, a thin layer of tumors may remain outside of the resection process due to the possibility of permanent injury; these residual tumors expose patients to the risk of tumor recurrence. This study has introduced the use of microneedle patches implanted after surgery with a dual-release mechanism for the administration of doxorubicin. The proposed patches possess the capability to administer drugs directly to the residual tumors and initiate chemotherapy immediately following surgical procedures. Three-dimensional simulation of drug delivery to residual tumors in the brain has been performed based on a finite element method. The impact of four important parameters on drug delivery has been investigated, involving the fraction of drug released in the burst phase, the density of microneedles on the patch, the length of microneedles, and the microvascular density of the tumor. The simulation findings indicate that lowering the fraction of drug released in the initial burst phase reduces the maximum average concentration, but the sustained release that continues for a longer period, increasing the bioavailability of free drug. However, the area under curve (AUC) for different release rates remains unchanged due to the fact that an identical dose of drug is supplied in each instance. By increasing the density of microneedles on the patch, concentration accumulation is provided over an extensive region of tumor, which in turn induces more cancer cell death. A comparative analysis of various lengths reveals that longer microneedles facilitate profound penetration into the tumor layers and present better therapeutic response due to extensive area of the tumor which is exposure to chemotherapeutic drugs. Furthermore, high microvascular density, as a characteristic of the tumor microenvironment, is shown to have a significant impact on the blood microvessels drainage of drugs and consequently lower therapeutic response outcome. Our approach offers a computational framework for creating localized drug delivery systems and addressing the challenges related to residual brain tumors.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1567-1594"},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}